The objectives of radiotherapy is to eradicate a malignancy without producing unacceptable complications. Thus to predict the likelihood of success of any therapeutic strategy, one must be able to assess the effects of X-irradiation upon both diseased and healthy tissue. The present work explores a means of estimating, for a given spatial and temporal distribution of radiation dose, the probability of inducing severe complications in a healthy organ or tissue. These estimates are made from dose-volume histograms derived from the treatment plan which has been calculated for the total irradiated volume. The estimates of complication probabilities are to be correlated with the complication experience obtained from patients treated at the Lawrence Berkeley Laboratory. The aim is to establish which of the normal tissues are amenable to this type of analysis and for those tissues, the validity of the tolerance dose values which are assumed to apply. The approach has been recently developed for the optimization of treatment plans for heavy particle beam therapy, as part of a NCI contract for the "Evaluation of Particle Beam Treatment Planning". It is however equally applicable to all modalities of conventional external beam radiotherapy, and possibly elsewhere as well. The clinical validation of the estimated complication probability would aid in adoption of a new method for treatment plan optimization.